4-Methylmorpholine → HCID 23289893, compound

HRID 366796Notes

Reaction equation

HRID 366796 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[CH:6]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[C:7]3[N:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][N:10]([CH3:11])[C:4]=2[CH:3]=1.[CH3:24][C:25]([CH3:40])([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([CH2:36][C:37](O)=[O:38])[CH2:32][CH2:31]1)=[O:29])[CH3:26].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.O>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[CH:6]([N:16]3[CH2:21][CH2:20][N:19]([C:37](=[O:38])[CH2:36][CH:33]4[CH2:34][CH2:35][N:30]([C:28]([O:27][C:25]([CH3:26])([CH3:24])[CH3:40])=[O:29])[CH2:31][CH2:32]4)[CH2:18][CH2:17]3)[C:7]3[N:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][N:10]([CH3:11])[C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1512539[1-(tert-Butoxycarbonyl)piperidin-4-yl]acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23289852HCID 23289852, compound

Product 1

HCID 23289893HCID 23289893, compoundYield 30.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

(8-Chloro-6,11-dihydro-6-methyl-5H-pyrido[3,2-c][1]benzazepin-11-yl)-piperazine (531 mg, 1.14 mmol), 1-(1,1-dimethylethoxycarbonyl)-4-piperidine-acetic acid (570 mg, 2.3 mmol), EDCl (439 mg) and HOBT (311mg) were dissolved in DMF (8 ml), and NMM (4 ml) was added. The reaction mixture was stirred at 20° C. for 20 hours and then water (100 ml) was added, and the resulting tan suspension was extracted with EtOAc (2×30 ml). The EtOAc phase was then washed with Na2CO3 (30 ml), dried over Na2SO4, filtered, and evaporated. The product was chromatographed over silica gel in CH2Cl2, and the column was eluted with CH2Cl2 and with CH2Cl2 /MeOH (95:5). The resulting purer material (0.75 g) was rechromatographed over silica gel in hexane/acetone (85:15) and eluted with increasing amounts of acetone (finally 30%). The product was rechromatographed on silica gel to afford the title compound (0.19 g), m.p. 86-98° C.; found: C, 64.64; H, 7.39; N, 12.12; calcd. for C30H40ClN5O3 : C, 65.03; H, 7.28; N, 12.64; HRMS: calcd. 554.2898; found 554.2891.

Workup

  1. extractionthe resulting tan suspension was extracted with EtOAc (2×30 ml)
  2. washThe EtOAc phase was then washed with Na2CO3 (30 ml)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe product was chromatographed over silica gel in CH2Cl2
  7. washthe column was eluted with CH2Cl2 and with CH2Cl2 /MeOH (95:5)
  8. customThe resulting purer material (0.75 g) was rechromatographed over silica gel in hexane/acetone (85:15)
  9. washeluted with increasing amounts of acetone (finally 30%)
  10. customThe product was rechromatographed on silica gel

Sources & evidence

ORD record
ord-40689a9f221b4c788868ad08bcf73bcd
Source dataset
uspto-grants-2000_10
Patent number
US06130229

Reaction notes

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